The present invention relates to a strontium-rubidium infusion system. In particular, it relates to a strontium-rubidium infusion system which has an in-line, real time dosimetry system which can be used to infuse patients with Rubidium-82.
Current statistics show that approximately one-third of all deaths in the United States are related to coronary artery disease. See, for example, Pohost, G., McKusick, K., and Strauss, W., "Physiologic Basis and Utility of Myocardial Perfusion Imaging" Proceedings of the Second International Symposium on Radiopharmaceuticals, Society of Nuclear Medicine, New York 1979, pp. 465-473, and this fact has prompted extensive research to more efficiently diagnose and manage this disease. Recent advances in radiopharmaceutical development and instrument design have established myocardial scintigraphy as an important new approach for evaluating coronary artery disease and myocardial perfusion. See, for example, Pierson, R., Friedman, M., Tansley, W., Castellana, F., Enlander, D., and Huang, P., "Cardiovascular Nuclear Medicine: An Overview", Sem. Nucl. Med., 9, 224-240 (1979); Leppo, J., Scheuer, J., Pohost, G., Freeman, L., and Strauss, H., "The Evaluation of Ischemic Heart Disease Thallium-201 with Comments on Radionuclide Angiography"; Sem. Nucl. Med., 10, 115-126 (1980); Vogel, R., "Quantitative Aspects of Myocardial Perfusion Imaging", Sem. Nucl. Med., 10, 146-156 (1980); Chervu, R., "Radiopharmaceuticals in Cardiovascular Nuclear Medicine", Sem. Nucl. Med., 9, 241-256 (1979); and Pitt. B., and Strauss, H., "Cardiovascular Nuclear Medicine", Sem. Nucl. Med., 7, 3-6 (1977).
Myocardial scintigraphy studies have been performed with several isotopes of potassium, rubidium, cesium, and thallium (T1-201), although the usefulness of all of these nuclides is limited by their non-optimal physical properties. In spite of its long half-life andlow-gamma energy, T1-201 is currently the most widely used agent for myocardial imaging. See, for example, Poe, N., "Rationale and Radiopharmaceuticals for Myocardial Imaging", Sem. Nucl. Med., 7, 7-14 (1977); Strauss, H. and Pitt, B., "Thallium-201 as a Myocardial Imaging Agent", Sem. Nucl. Med., 7, 49-58 (1977); Botvinick, E., Dunn. R., Hattner, R., and Massie, B., "A Consideration of Factors Affecting the Diagnostic Accuracy of T1-201 Myocardial Perfusion Scintigraphy in Detecting Coronary Artery Disease", Sem. Nucl. Med., 10, 157-167 (1980); and Wackers, F., "Thallium-201 Myocardial Scintigraphy in Acute Myocardial Infarction and Ischemia", Sem. Nucl. Med., 10, 127-145 (1980).
In diagnostic procedures in which the heart is involved, it is desirable for a diagnostician to be able to view a patient's heart. Heretofore, various radioactive materials have been used together with radiological procedures for viewing internal organs of patients. It has been difficult, however, to view a heart because the radioactive substances which could be used for viewing the heart have had a very long half-life. Thus, using them with patients involves an element of danger and also reduces the number of times that a patient could be infused within any given time period. It would therefore be desirable to have a diagnostic apparatus and procedure which could be used with relative safety for viewing the heart.
Rubidium-82 is a potassium analog. That means it acts similar to potassium which it is infused into a patient. Thus it builds up at a very rapid rate, i.e., within seconds, in the patient's heart. Rubidium-82 also has the advantage of having a very short half-life, approximately 76 seconds. Therefore, it decays after a very short period of time following entry into the body, thereby allowing numerous procedures to be performed within a relatively short time period in a given patient. Rubidium-82 also has the advantage of being observable using a modified gamma camera such as a gamma camera of the type manufactured by Searle Radiographics, Inc., called the PHO Gamma IV. A problem with using Rubidium-82 in a patient involves keeping track of the amount of radiation infused into the patient. In view of the very short half-life of Rubidium-82, it is impractical to measure the radioactivity of a particular dose and to then infuse it into the patient using conventional means. An accurate method for measuring the amount of radiation being infused into the patient would be highly desirable for this particular application.
The availability of improved instrumentation has stimulated interest in the use of the positron emitter, Rubidium-82, for myocardial imaging. See for example, Beller G., and Smith, T., "Radionuclide Techniques in the Assessment of Myocardial Ischemia and Infarction," Circulation, 53 (3, Supp. 1) 123-125 (1976); Budinger, T., Yano, Y., Derenzo, S., et al., "Myocardial Uptake of Rubidium-82 Using Positron Emission Tomography," J., Nucl. Med. 20, 603 (1979); Budinger, T., Yano, Y., Derenzo, S., et al., "Infarction Sizing and Myocardial Perfusion Measurements Using Rb-82 and Positron Emission Tomography," Amer. J. Cardiol., 45, 399 (1980). Rubidium-82, an analog of the alkali metal potassium, is rapidly cleared from the blood and concentrated by the myocardium. The short half-life of the Rubidium-82 (76 sec) offers the unique advantage of permitting repeat perfusion and blood flow studies in patients whose clinical status is rapidly changing.
Rubidium-82 is produced by the decay of its parent, strontium-82. E. R. Squibb and Sons, Inc. has developed a Rubidium-82 generator and infusion system which yields an isotonic saline solution of Rubidium-82 at physiological pH for rapid administration. In animal experiments, the safety and myocardial uptake of Rubidium-82 has been demonstrated. Therefore this agent has been selected as a candidate for clinical trials.